Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice.

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

Protective effects of andrographolide sodium bisulfate on UV-induced skin carcinogenesis in mice model.

Although the mortality of skin cancer patients is relatively low, there are still a large number of patients died of these tumors at high incidence rate. Chronic exposure to solar UV irradiation is the most common cause of nonmelanoma skin tumors. Our research aimed to explore the effects of andrographolide sodium bisulfate (ASB) on UV-induced skin cancer and to reveal the underlying molecular mechanism. In the present study, histopathology changes, immunohistochemical analysis, ELISA analysis and western blot analysis were mainly used in vivo. The results indicated that ASB significantly inhibited increase of skin epidermal thickness, inflammatory cells infiltration and fibers damage in dermis, oxidative stress injury and skin carcinogenesis. Moreover, the western blot analysis showed that protein expressions of NF-κB, Nrf2, p62, LC3 II/I and p-p62 (Ser 349) in mouse skin induced by UV were dramatically suppressed in the ASB-pretreated groups. Overall, these results suggested that ASB exerted a strong preventive effect and potential therapeutic value against UV-induced skin carcinogenesis in mice through inhibiting NF-κB and Nrf2 signaling pathways and restoring autophagy.

Gender differences in UV-induced skin inflammation, skin carcinogenesis and systemic damage.

Ultraviolet (UV) radiation-induced chronic inflammation contributes to all stages of skin tumor development. In addition, gender plays an important role in inflammatory diseases or cancer. In this study, histopathology changes, hematology, oxidative stress and inflammatory response were used to evaluate sex differences in UV-induced chronic inflammation-associated cancer development. The results showed that the male and female mice had photoaging damage at the 9th week. However, skin tumors only appeared in male mice at 31st week. Furthermore, UV increased ROS production, p65, p-p65, IL-6 and TNF-α protein expressions in skin, and these factors elevated more in male mouse model. Hematology results showed that the parameters of blood systemic inflammation were changed in different degrees in model groups, while the pathological results showed inflammatory cell infiltration in the internal organs of both model groups in varying degrees. These results indicate that there are gender differences in UV-induced skin inflammation, carcinogenesis and systemic damage. Moreover, male mice are more sensitive to UV irradiation, which may be responsible to greater oxidative stress and inflammatory damage.

Andrographolide sodium bisulfate attenuates UV­induced photo­damage by activating the keap1/Nrf2 pathway and downregulating the NF­κB pathway in HaCaT keratinocytes.

Oxidative and inflammatory damage has been suggested to play important roles in the pathogenesis of skin photoaging. Andrographolide sodium bisulfate (ASB) is a soluble derivative of andrographolide and has known antioxidant and anti­inflammatory properties. In the present study, cellular experiments were designed to investigate the molecular mechanisms underlying the effect of ASB in relieving ultraviolet (UV)­induced photo­damage. Following ASB pretreatment and UV irradiation, the apoptosis and necrosis of HaCaT cells were investigated by Hoechst 33342/propidium iodide staining. Reactive oxygen species (ROS) production was investigated using a DCFH­DA fluorescence probe. Furthermore, the protein expression levels of p65, NF­κB inhibitor­α, nuclear factor E2­related factor 2 (Nrf2) and kelch­like ECH­associated protein 1 (keap1) were measured via western blotting and immunofluorescence analyses. Furthermore, NF­κB­mediated cytokines were assessed by ELISA, and Nrf2­mediated genes were detected by reverse transcription­quantitative PCR. Pretreatment with ASB markedly increased cell viability, decreased cell apoptosis and decreased UV­induced excess ROS levels. In addition, ASB activated the production of Nrf2 and increased the mRNA expression levels of glutamate­cysteine ligase catalytic subunit and NAD(P)H quinone oxidoreductase 1, while ASB downregulated the protein expression of p65 and decreased the production of interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α. These results suggested that ASB attenuates UV­induced photo­damage by activating the keap1/Nrf2 pathway and downregulating the NF­κB pathway in HaCaT keratinocytes.